目的:通过研究不同浓度的川芎嗪(tertramethylpyrazine,TMP)在大鼠肾脏缺血再灌注损伤过程中的作用,探讨川芎嗪对肾脏组织发挥保护作用的最佳浓度。方法:建立大鼠肾脏缺血再灌注模型,分别检测假手术组、模型组、川芎嗪用药组(川芎嗪15,30,45,60,90 mg·kg~(-1))血肌酐(Cr)和尿素氮(BUN)水平,观察肾组织形态并测定其中的诱导型一氧化氮合酶(induced nitric oxide synthase,iNOS)活性。结果:15 mg·kg~(-1)和30 mg·kg~(-1)组川芎嗪显著降低肾组织内iNOS的活性,降低血浆Cr和BUN水平,减轻肾小管上皮细胞坏死程度,以15 mg·kg~(-1)最为显著;45 mg·kg~(-1)组血Cr和BUN水平及肾小管坏死程度低于模型组,但高于假手术组,且均有显著性差异;60 mg·kg~(-1)组和90 mg·kg~(-1)组血Cr和BUN反而上升,小管上皮细胞坏死比模型组明显加重,肾组织内iNOS较模型组变化不明显。结论:合适剂量(15～45 mg·kg~(-1))的川芎嗪可以通过降低iNOS活性,保护缺血再灌注肾功能,减轻肾组织病理损害,以15 mg·kg~(-1)最为显著,随剂量增加保护作用减弱。而较高浓度(45～90 mg·kg~(-1))川芎嗪失去对缺血再灌注肾脏的保护作用。 OBJECTIVE: To study the effects of different concentrations of tertramethylpyrazine (TMP) on renal ischemia-reperfusion injury in rats and to explore the optimal concentration of tetramethylpyrazine for protecting kidney tissues. METHODS: Rat kidney ischemia-reperfusion model was established. Serum creatinine (Cr) in sham-operated group, model group, and Ligustrazine group (tetramethylpyrazine 15, 30, 45, 60, 90 mg·kg -1) was measured. ) and BUN levels were observed in renal tissue and the inducible nitric oxide synthase (iNOS) activity was measured. RESULTS: Ligustrazine in the 15 mg·kg -1 and 30 mg·kg -1 groups significantly decreased the activity of iNOS in renal tissues, decreased the levels of plasma Cr and BUN, and reduced the degree of necrosis of renal tubular epithelial cells. The concentration of mg·kg -1 was the most significant; the blood Cr and BUN levels and tubular necrosis were lower in the 45 mg·kg -1 group than in the model group, but higher than the sham operation group, and there were significant differences. In the 60 mg·kg -1 group and 90 mg·kg -1 group, blood Cr and BUN increased but the necrosis of tubular epithelial cells was significantly heavier than that in the model group. The iNOS in the renal tissue did not change significantly compared with the model group. Conclusion: Ligustrazine at a proper dose (15-45 mg·kg -1 ) can reduce the iNOS activity, protect the renal function of ischemia-reperfusion, and reduce the renal pathological damage to 15 mg·kg -1 The most significant, with the dose increase protection weakened. The higher concentration (45-90 mg·kg -1 ) of tetramethylpyrazine lost its protective effect on renal ischemia-reperfusion injury.